Safety and efficacy evaluation of low-dose trimethoprim-sulfamethoxazole for prophylaxis of Pneumocystis pneumonia in HIV uninfected patients undergoing hemodialysis: a retrospective observational study.

BACKGROUND: Pneumocystis pneumonia (PCP) is a potentially life-threatening infection. Trimethoprim-sulfamethoxazole (TMP-SMX) is considered as the first regimen for PCP prophylaxis according to several guidelines. The recommended prophylactic dose of TMP-SMX has been determined based on patients with normal renal function, but the appropriate dosage for patients undergoing hemodialysis is unknown. The aim of this study was to investigate the efficacy and safety of low-dose TMP-SMX in patients undergoing hemodialysis. METHODS: HIV-uninfected adult patients who were undergoing hemodialysis and administered TMP-SMX for PCP prophylaxis, were included, and divided into standard-dose (≥6 single strength (SS, TMP-SMX 80 mg/400 mg tablets/week) and low-dose groups (< 6 SS tablets/week). The endpoints were cumulative incidence of PCP and cumulative discontinuation rate of TMP-SMX due to adverse events. For comparison of the groups, we employed the chi-squared test for categorical variables and the Mann-Whitney U test for continuous variables. Risk factors for the endpoints were evaluated using the Cox Fine and Gray method. RESULTS: The median age of the 81 patients included in the study was 67 years (IQR: 60-76 years), and 52 patients (64.2%) were men. No patients in either group developed PCP during the observation period. The yearly cumulative incidence of discontinuation was 12.1% (95% confidence interval [CI]: 0.027-0.29) in the low-dose group and 35.6% (95% CI: 0.20-0.52) in the standard-dose group (P = 0.019). The adjusted hazard ratio of the low-dose group compared to standard-dose group was 0.18 (95% CI: 0.04-0.86, P = 0.032). CONCLUSIONS: None of the study patients developed PCP, and the cumulative discontinuation rate of TMP-SMX due to adverse events was significantly lower in the low-dose group compared to that in the standard-dose group (P = 0.032). These results indicate that low-dose TMP-SMX is an appropriate regimen to maintain a balance between PCP prophylaxis and prevention of adverse events due to TMP-SMX administration. These findings can guide health care professionals to determine TMP-SMX dosage when considering PCP prophylaxis for patients undergoing hemodialysis.

Comparison of quality of life and activity of daily living status of patients with myasthenia gravis treated with low-dose and high-dose prednisolone.

OBJECTIVES: To compare the effect of low-dose prednisolone (PSL) (≤5 mg/day) and high-dose PSL (>5 mg/day) therapy on the QOL and activity of daily living (ADL) in patients with MG. METHODS: A total of 679 patients with MG underwent a survey using Japanese versions of the MG-QOL 15-J and MG-ADL scales. Higher scores of these scales suggest deterioration of the QOL and ADL, respectively. RESULTS: The total MG-QOL 15-J scores of the high-dose group (27.0±13.8) were significantly higher than those of the low-dose group (20.9±14.6). Similarly, the total MG-ADL scores of the high-dose group (6.3±4.1) were significantly higher than those of the low-dose group (5.3±4.1). CONCLUSION: These results showed that the QOL of patients in the low-dose group appeared better than that in the high-dose group. Low-dose PSL therapy may help achieve minimal manifestations level in Japanese patients with MG.

pspK acquisition contributes to the loss of capsule in pneumococci: molecular characterisation of non-encapsulated pneumococci.

With the introduction of the pneumococcal conjugate vaccine (PCV), the number of cases of non-vaccine type pneumococci and non-encapsulated Streptococcus pneumoniae (NESp) infection have increased. In order to clarify how pspK-harbouring NESp might have emerged, we characterised NESp and analysed the correlation between transformation and non-encapsulation. A total of 26 NESp strains were used in this study. The genetic backgrounds were compared using multilocus sequence typing (MLST). The ΔpspK::ermB strain, in which pspK was replaced by ermB in NESp, was constructed by homologous recombination. The genomic DNA of the ΔpspK::ermB strain was transformed into two types of encapsulated S. pneumoniae via transformation. The fitness of the parent and non-encapsulated transformants was compared using the growth curve. All NESp had pspK instead of capsular coding regions and were classified into 14 types by MLST, which indicated that NESp had several genetic backgrounds. Transformation of ΔpspK::ermB genomic DNA resulted in 10-4‒10-5 non-encapsulated transformants. Non-encapsulated transformants could grow faster than the encapsulated parent strain. The acquisition of pspK region via transformation contributed to the loss of encapsulation with high frequency. The present results suggest that non-encapsulation through pspK acquisition could be a potential mechanism to evade PCV.

Stress and coping styles in Japanese nursing students.

The objective of this investigation was to examine the stress and coping styles in Japanese nursing students. The principal measures of the stress and coping styles were the General Health Questionnaire (GHQ)-12 and Brief Coping Orientations to Problems Experienced scale. In a cross-sectional analysis, 1324 students completed the anonymous self-administered questionnaires including the scales earlier. Feeling stress, living with family, not eating breakfast every day, having no regular exercise and poor sleep were associated with GHQ responder (psychological distressed group). The most commonly reported source of stress was taking examinations, followed by relationships with friends, engaging in clinical practice and presenting reports. The three most common coping styles adopted by the nursing students were acceptance, self-distraction and using instrumental support. By logistic regression analysis of coping styles with GHQ responder, self-blame, active coping, acceptance and behavioural disengagement were highly associated with GHQ responder. The nursing school educators as well as students should be aware of stress management strategies (e.g. using active coping and avoiding self-blame) that may help prevent depression.

Dietary tocotrienol reduces UVB-induced skin damage and sesamin enhances tocotrienol effects in hairless mice.

We have previously reported that substantial amounts of tocotrienols were present in the skin of animals fed a diet containing a tocopherols and tocotrienols rich fraction (T-mix) extracted from palm oil, and further, that sesame lignans enhanced tocotrienol levels in the skin. The present studies were undertaken to determine whether dietary tocotrienols and those with sesamin could protect the skin from damage induced by UVB irradiation in hairless mice fed four diets: a vitamin E-free diet, a 50 mg/kg alpha-tocopherol diet, a 229 mg/kg T-mix (with 50 mg alpha-tocopherol) diet and a 229 mg/kg T-mix with 2 g/kg sesamin diet. In Experiment 1, mice were fed the diets for 6 wk, and half of the mice were exposed to 180 mJ/cm(2 )of UVB light once daily for 7 d. After the intensity of sunburn was scored, vitamin E and thiobarbituric acid reactive substances (TBARS) concentrations in the skin and liver were determined. In Experiment 2, hairless mice were initiated with a single application of 7, 12-dimethylbenz[a]anthracene (DMBA), then 1 wk later mice were fed the experimental diets and subjected to 180 mJ/cm(2) UVB irradiation twice weekly for 20 wk. Tumor incidences were counted once a week. Tocotrienols were detected in the skin of mice fed T-mix, but their concentrations were significantly lower than for alpha-tocopherol. Sesamin elevated tocotrienol contents in the skin. In spite of the high alpha-tocopherol contents, the effects of alpha-tocopherol on sunburn and incidence of tumor were slight. T-mix fed groups reduced the extent of sunburn and incidence of tumor, and further reduction of sunburn and incidence of tumor were observed in the T-mix with sesamin group. These results suggest that dietary tocotrienols protect the skin more strongly than alpha-tocopherol against damage induced by UVB and sesamin enhances tocotrienol effects.

Hydroxymatairesinol and sesaminol act differently on tocopherol concentrations in rats.

We have previously reported that sesame seed with the tetrahydrofurofuran type lignans sesamin and sesaminol (SeOH) produced higher tocopherol concentrations, while flaxseed with the dibenzylbutyrolactone type lignans did not cause higher tocopherol concentrations in rats. Sesame seeds also contain the dibenzylbutyrolactone type lignan 7-hydroxymatairesinol (HMR). To clarify whether or not the tocopherol elevating effect is affected by the chemical structure of lignans, the effect of HMR isolated from Norway spruce, was compared with SeOH, isolated from sesame seed. The lignans were added to a low alpha-tocopherol (10 mg/kg) diet, and rats were maintained on these diets for 8 wk. The experimental diet containing 0.2% SeOH elevated alpha-tocopherol content in the plasma liver, kidney, and brain, but HMR (0.2% or 0.5%) had no effects. Dietary HMR and SeOH (both in concentrations of 0.2%) were further compared in rats fed on a gamma-tocopherol (50 mg/kg) containing diet. SeOH produced significantly higher g-tocopherol content in the plasma and tissues, and significantly lower 2,7,8-trimethyl-2(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC, a gamma-tocopherol metabolite) content in the urine. However, HMR did not show such effects. These results suggest that the sesame lignan SeOH increases tocopherol concentrations in animals by suppressing the conversion of gamma-tocopherol to gamma-CEHC. HMR, a structurally different plant lignan, does not have such properties. Further studies are needed to show the potential health effects associated with an increased tocopherol concentration in the body.

Dietary sesame seed and its lignan increase both ascorbic acid concentration in some tissues and urinary excretion by stimulating biosynthesis in rats.

We previously showed that the intake of sesamin, a major lignan in sesame seed, decreased lipid peroxidation and elevated tocopherol concentration in rat tissues. In this study, we examined the effect of dietary sesame seed and sesamin on the ascorbic acid concentration in rat tissues. Rats (4-wk-old) were fed either a vitamin E-free diet, or a diet containing 50 mg gamma-tocopherol/kg, one containing 2 g sesamin/kg, one containing 50 mg gamma-tocopherol/kg and 2 g sesamin/kg, or one containing 200 g sesame seed/kg for 28 d. The dietary sesamin and sesame seed elevated ascorbic acid concentrations in the liver and kidney, and increased urinary excretion in those Wistar rats. The dietary sesamin also elevated the hepatic mRNA levels of cytochrome P450 (CYP) 2B, and UDP-glucuronosyltransferase (UGT) 1A and 2B. In contrast, neither the sesamin nor the sesame seed affected the liver concentration of ascorbic acid in ODS rats with a hereditary defect in ascorbic acid synthesis, though the dietary sesame seed elevated the UGT1A and 2B mRNA levels in the liver. In addition, the sesame seed elevated the gamma-tocopherol concentration in the various ODS rat tissues and the ascorbic acid concentrations in the kidney, heart and lung, while reducing the thiobarbituric acid reactive substance concentration in the heart and kidney. These results suggest that dietary sesame seed and its lignan stimulate ascorbic acid synthesis as a result of the induction of UGT1A and the 2B-mediated metabolism of sesame lignan in rats. The data of ODS rat studies also suggest that dietary sesame seed enhances antioxidative activity in the tissues by elevating the levels of two antioxidative vitamins, vitamin C and E.

Dietary sesame seed decreases urinary excretion of alpha- and gamma-tocopherol metabolites in rats.

We previously showed that dietary sesame seed and its lignan inhibited gamma-tocopherol metabolism to 2,7,8-trimethyl-2(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC), a gamma-tocopherol metabolite, and markedly elevated tissue gamma-tocopherol concentration in rats. The aim of this study was to clarify the effect of dietary sesame seed on alpha-tocopherol metabolism. Vitamin E-deficient rats fed a vitamin E-free diet for 4 wk were fed a diet containing alpha-tocopherol, alpha- and gamma-tocopherol, or alpha-tocopherol with sesame seed for 7 d. Urinary excretion of 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman (alpha-CEHC), a alpha-tocopherol metabolite, in rats fed alpha-tocopherol with sesame seed was inhibited (p<0.05) as compared with that in rats fed alpha-tocopherol alone, or alpha- and gamma-tocopherol. The gamma-CEHC excretion was also less (p<0.05) in rats fed alpha-tocopherol with sesame seed than that in rats fed alpha- and gamma-tocopherol. The inhibition of alpha- and gamma-CEHC excretion by sesame seed was accompanied by elevation (p<0.05) of the alpha- and gamma-tocopherol concentration in the liver. These results suggest that dietary sesame seed inhibits not only gamma-tocopherol metabolism to gamma-CEHC but also alpha-tocopherol metabolism to alpha-CEHC in rats.

Cytochrome P450-dependent metabolism of vitamin E isoforms is a critical determinant of their tissue concentrations in rats.

The aim of this study was to clarify the contribution of cytochrome P450 (CYP)-dependent metabolism of vitamin E isoforms to their tissue concentrations. We studied the effect of ketoconazole, a potent inhibitor of CYP-dependent vitamin E metabolism in cultured cells, on vitamin E concentration in rats. Vitamin E-deficient rats fed a vitamin E-free diet for 4 weeks were administered by oral gavage a vitamin E-free emulsion, an emulsion containing alpha-tocopherol, gamma-tocopherol or a tocotrienol mixture with or without ketoconazole. Alpha-tocopherol was detected in the serum and various tissues of the vitamin E-deficient rats, but gamma-tocopherol, alpha- and gamma-tocotrienol were not detected. Ketoconazole decreased urinary excretion of 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman after alpha-tocopherol or a tocotrienol mixture administration, and that of 2,7,8-trimethyl-2(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC) after gamma-tocopherol or a tocotrienol mixture administration. The gamma-tocopherol, alpha- and gamma-tocotrienol concentrations in the serum and various tissues at 24 h after their administration were elevated by ketoconazole, while the alpha-tocopherol concentration was not affected. The gamma-tocopherol or gamma-tocotrienol concentration in the jejunum at 3 h after each administration was also elevated by ketoconazole. In addition, significant amount of gamma-CEHC was in the jejunum at 3 h after gamma-tocopherol or gamma-tocotrienol administration, and ketoconazole inhibited gamma-tocopherol metabolism to gamma-CEHC in the jejunum. These results showed that CYP-dependent metabolism of gamma-tocopherol and tocotrienol is a critical determinant of their concentrations in the serum and tissues. The data also suggest that some amount of dietary vitamin E isoform is metabolized by a CYP-mediated pathway in the intestine during absorption.

Triton WR1339, an inhibitor of lipoprotein lipase, decreases vitamin E concentration in some tissues of rats by inhibiting its transport to liver.

The aim of this experiment was to clarify the contribution of the alpha-tocopherol transfer activity of lipoprotein lipase (LPL) to vitamin E transport to tissues in vivo. We studied the effect of Triton WR1339, which prevents the catabolism of triacylglycerol-rich lipoproteins by LPL on vitamin E distribution in rats. Vitamin E-deficient rats fed a vitamin E-free diet for 4 wk were injected with Triton WR1339 and administered by oral gavage an emulsion containing 10 mg of alpha-tocopherol, 10 mg of gamma-tocopherol, or 29.5 mg of a tocotrienol mixture with 200 mg of sodium taurocholate, 200 mg of triolein, and 50 mg of albumin. alpha-Tocopherol was detected in the serum and other tissues of the vitamin E-deficient rats, but gamma-tocopherol, alpha- and gamma-tocotrienol were not detected. Triton WR1339 injection elevated (P<0.05) the serum alpha-tocopherol concentration and inhibited (P<0.05) the elevation of alpha-tocopherol concentration in the liver, adrenal gland, and spleen due to the oral administration of alpha-tocopherol. Neither alpha-tocopherol administration nor Triton WR1339 injection affected (P>or=0.05) the alpha-tocopherol concentration in the perirenal adipose tissue, epididymal fat, and soleus muscle despite a high expression of LPL in the adipose tissue and muscle. These data show that alpha-tocopherol transfer activity of LPL in adipose tissue and muscle is not important for alpha-tocopherol transport to the tissue after alpha-tocopherol intake or that the amount transferred is small relative to the tissue concentration. Furthermore, Triton WR1339 injection tended to elevate the serum gamma-tocopherol (P=0.071) and alpha-tocotrienol (P=0.053) concentrations and lowered them (P<0.05) in the liver and adrenal gland of rats administered gamma-tocopherol or alpha-tocotrienol. These data suggest that lipolysis of triacylglycerol-rich chylomicron by LPL is necessary for postprandial vitamin E transport to the liver and subsequent transport to the other tissues.

Dietary sesame seeds elevate alpha-tocopherol concentration in rat brain.

We have previously reported that dietary sesame lignan elevates alpha-tocopherol concentration and decreases lipid peroxidation in tissues and serum of rats fed alpha-tocopherol. In this study, the effect of dietary sesame seeds on alpha-tocopherol concentration and lipid peroxidation in rat brain was examined. In experiment 1, male Wistar rats (4 wk old) were fed a vitamin E-free diet, or a diet containing alpha-tocopherol with or without sesame seeds for 1, 4 and 8 wk. The dietary sesame seeds elevated the alpha-tocopherol and lowered the thiobarbituric acid-reactive substance (TBARS) concentrations in the brain of the rats fed alpha-tocopherol for 4 and 8 wk. The dietary sesame seeds maintained the high alpha-tocopherol concentration in the brain during the experimental period, while the concentration of the rats fed alpha-tocopherol without sesame seeds was lowered after 8 wk. Then, the alpha-tocopherol concentration in various regions of the brain of rats fed a basal level of alpha-tocopherol with sesame seeds was compared with that of rats fed an excess amount of alpha-tocopherol in experiment 2. The alpha-tocopherol concentration in the cerebrum, cerebellum, brain stem and hippocampus of the rats fed 50 mg alpha-tocopherol/kg with sesame seeds was higher than those of the rats fed 500 mg alpha-tocopherol/kg without sesame seeds. These results suggest that the dietary sesame seeds are more useful than the intake of an excess amount of alpha-tocopherol, for maintaining a high alpha-tocopherol concentration and inhibiting lipid peroxidation in the various regions of the rat brain.

Absorption and excretion of the 8-hydroxydaidzein in rats after oral administration and its antioxidant effect.

8-Hydroxydaidzein (8-OHD), which is produced during the processing of fermented soybean products, has a potent antioxidant activity in vitro. There is no information regarding the absorption and excretion of this isoflavone, including its antioxidant effect in vivo. In this study, rats were administered a single oral dose of 8-OHD (20 mg/kg body weight), and the blood, liver, kidney and urine were collected at specific intervals up to 18 h after dosing. Free 8-OHD in each tissue was directly determined by using HPLC with electrochemical detection, while its conjugates were detected after the treatment with beta-glucuronidase and sulfatase. The total 8-OHD in liver reached a high level (9.4 nmol/g) at 1 h after dosing, and maintained the relatively high concentration up to 10 h. Most of the 8-OHD was present in free form in liver, while the majority of 8-OHD in plasma was conjugated. This suggests that free 8-OHD in liver is successively converted to glucuronide and/or sulfate and the conjugated 8-OHD is released into the blood. The maximum level of total 8-OHD in plasma or kidney was observed within the first 2 h after the oral administration. The level of 8-OHD in these tissues gradually decreased within the further experiments. Excretion of the 8-OHD in urine began to rise at 1-2 h interval. The mean urinary excretion rate of 8-OHD showed a higher level at 2-4 h and 4-6 h intervals, while the 8-OHD levels at these intervals in plasma or kidney more rapidly decreased. The cumulative recovery of 8-OHD in the urine over the 0-18 h interval was about 36% of the dose. In addition, the liver homogenate from rats killed at 1 h and 2 h after dosing, which contained a higher level of free 8-OHD, showed a significantly lower susceptibility to lipid peroxidation induced by AAPH or Cu2+ than that at 0 h (pre-administered rats). These results suggest that 8-OHD was relatively easily absorbed into rats and might exert its biological activities in vivo, including the antioxidant effect.

Dietary sesame lignans decrease lipid peroxidation in rats fed docosahexaenoic acid.

We have previously reported that dietary sesamin and sesaminol, major lignans of sesame seed, elevate the alpha-tocopherol concentration and decrease the thiobarbituric acid reactive substance (TBARS) concentration in the plasma and liver of rats. In this study, the effects of dietary sesamin and sesaminol on the lipid peroxidation in the plasma and tissues of rats fed docosahexaenoic acid (DHA, 22:6 n-3) were examined. Male Wistar rats (4-wk-old) were divided into the following six experimental groups: control group, fed a basal diet: sesamin group, fed a diet with sesamin (2 g/kg); sesaminol group, fed a diet with sesaminol (2 g/kg); DHA group, fed a diet containing DHA (5 g/kg); DHA + sesamin group, fed a diet containing DHA with sesamin; and DHA + sesaminol group, fed a diet containing DHA with sesaminol. Each diet contained either 0.01 or 0.05 g D-alpha-tocopherol/kg, and the rats were fed the respective experimental diet for 5 wk. The dietary DHA elevated the TBARS concentration and also increased the red blood-cell hemolysis induced by the dialuric acid. The dietary sesamin and sesaminol lowered the TBARS concentrations and decreased the red blood hemolysis. The dietary sesamin and sesaminol elevated the alpha-tocopherol concentrations in the plasma, liver, and brain of the rats fed a diet with or without DHA. These results suggest that dietary sesame lignans decrease lipid peroxidation as a result of elevating the alpha-tocopherol concentration in rats fed DHA.

Dietary alpha-tocopherol decreases alpha-tocotrienol but not gamma-tocotrienol concentration in rats.

We previously showed that alpha- and gamma-tocotrienols accumulate in adipose tissue and skin but not in plasma or other tissues of rats fed a tocotrienol-rich fraction extracted from palm oil containing alpha-tocopherol and alpha- and gamma-tocotrienols. To clarify the nature of tocotrienol metabolism, we studied the distribution of alpha- or gamma-tocotrienol in rats fed alpha- or gamma-tocotrienol without alpha-tocopherol, and the effect of alpha-tocopherol on their distribution. Wistar rats (4-wk-old) were fed a diet with 50 mg alpha-tocotrienol/kg alone or with 50 mg alpha-tocopherol/kg in expt. 1, and a diet with 50 mg gamma-tocotrienol/kg alone or with 50 mg alpha-tocopherol/kg in expt. 2, for 8 wk. alpha-Tocotrienol was detected in various tissues and plasma of the rats fed alpha-tocotrienol alone, and the alpha-tocotrienol concentrations in those tissues and plasma decreased (P < 0.05) by the dietary alpha-tocopherol in the rats fed alpha-tocotrienol with alpha-tocopherol. However, gamma-tocotrienol preferentially accumulated in the adipose tissue and skin of the rats fed gamma-tocotrienol alone, and the dietary alpha-tocopherol failed either to decrease (P >/= 0.05) gamma-tocotrienol concentrations in the adipose tissue and skin or to increase (P >/= 0.05) in the urinary excretion of 2,7,8-trimethyl-2(2'-carboxymethyl)-6-hydroxycroman, a metabolite of gamma-tocotrienol, in the rats fed gamma-tocotrienol with alpha-tocopherol. These data suggest that alpha-tocopherol enhances the alpha-tocotrienol metabolism but not the gamma-tocotrienol metabolism in rats.

Comparative effects of flaxseed and sesame seed on vitamin E and cholesterol levels in rats.

Flaxseed and sesame seed both contain more than 40% fat, about 20% protein, and vitamin E, mostly gamma-tocopherol. Furthermore, both contain considerable amounts of plant lignans. However, flaxseed contains 54% alpha-linolenic acid, but sesame seed only 0.6%, and the chemical structures of flaxseed and sesame lignans are different. In this study, we investigated the differential effects of flaxseed and sesame seed on plasma and tissue gamma-tocopherol, TBARS, and cholesterol concentrations. Rats were fed experimental diets for 4 wk: vitamin E-free, (-VE), gamma-tocopherol, flaxseed (FS), sesame seed (SS), flaxseed oil (FO), FO with sesamin (FOS), and defatted flaxseed (DFF). SS and FOS diets induced significantly higher gamma-tocopherol concentrations in plasma and liver compared with FS, FO, and DFF diets. Groups fed FS, FO, and FOS showed lower plasma total cholesterol compared with the SS and DFF groups. Higher TBARS concentrations in plasma and liver were observed in the FS and FO groups but not in the FOS group. These results suggest that sesame seed and its lignans induced higher gamma-tocopherol and lower TBARS concentrations, whereas flaxseed lignans had no such effects. Further, alpha-linolenic acid produced strong plasma cholesterol-lowering effects and higher TBARS concentrations.

Effect of sesaminol on plasma and tissue alpha-tocopherol and alpha-tocotrienol concentrations in rats fed a vitamin E concentrate rich in tocotrienols.

We have shown that sesame lignans added to rat diet resulted in significantly greater plasma and tissue concentrations of alpha- and gamma-tocopherol concentrations in supplemented rats than in rats without supplementation. In the present studies we examined whether sesaminol, a sesame lignan, enhances tocotrienol concentrations in plasma and tissues of rats fed diets containing a tocotrienol-rich fraction of palm oil (T-mix). In Experiment 1, effects of sesaminol on tocotrienol concentrations in plasma, liver, and kidney were evaluated in rats fed diets containing 20 mg/kg of T-mix (20T) and 50 mg/kg of T-mix (50T) with or without 0.1% sesaminol. Although the T-mix contained 23% alpha-tocopherol, 22% alpha-tocotrienol, and 34% gamma-tocotrienol, alpha-tocopherol constituted most or all of the vitamin E in plasma and tissue (from 97% in kidney to 100% in plasma), with no or very little alpha-tocotrienol and no gamma-tocotrienol at all. Addition of sesaminol to the T-mix resulted in significantly higher plasma, liver, and kidney alpha-tocopherol concentrations compared to values for T-mix alone. Further, T-mix with sesaminol resulted in significantly higher alpha-tocotrienol concentrations in kidney, although the concentration was very low. In Experiment 2, we examined whether sesaminol caused enhanced absorption of alpha-tocopherol and alpha-tocotrienol in a dosage regimen supplying T-mix and sesaminol on alternating days and observed significantly higher levels of alpha-tocopherol and alpha-tocotrienol in rats fed sesaminol, even without simultaneous intake, compared to those in rats without sesaminol. In Experiment 3, alpha-tocopherol was supplied to the stomach with and without sesaminol, and alpha-tocopherol concentrations in the lymph fluid were measured. a-Tocopherol concentrations were not different between groups. These results indicated that sesaminol produced markedly higher alpha-tocopherol concentrations in plasma and tissue and significantly greater alpha-tocotrienol concentrations in kidney and various other tissues, but the concentrations of alpha-tocotrienol were extremely low compared to those of a-tocopherol (Exps. 1 and 2). However, the sesaminol-induced increases of a-tocopherol and a-tocotrienol concentrations in plasma and tissue were not caused by their enhanced absorption since sesaminol did not enhance their absorption.

Dietary sesame seed and its lignans inhibit 2,7,8-trimethyl- 2(2'-carboxyethyl)-6-hydroxychroman excretion into urine of rats fed gamma-tocopherol.

We showed previously that dietary sesame seed and its lignans elevate the tocopherol concentration in rats. To clarify their effect on tocopherol metabolism, we determined in this study the urinary excretion of 2,7,8-trimethyl-2(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC), a gamma-tocopherol metabolite, in rats fed sesame seed or its lignans. Rats were fed diets with or without sesame seed for 28 d in Experiment 1, and for 1, 3 and 7 d in Experiment 2. On d 28, dietary sesame seed elevated (P < 0.05) gamma-tocopherol concentrations in liver, kidney, brain and serum, and decreased (P < 0.05) urinary excretion of gamma-CEHC. The excretion was completely inhibited by feeding sesame seed on d 1 and 3. In Experiment 3, the effects of dietary sesamin and sesaminol (major lignans in sesame seed) or ketoconazole (a selective inhibitor of cytochrome P(450) (CYP)3A on urinary excretion of gamma-CEHC in rats fed gamma-tocopherol were examined. The urinary gamma-CEHC in rats fed sesamin or sesaminol was markedly lower than in rats fed gamma-tocopherol alone (P < 0.05). Dietary ketoconazole also inhibited (P < 0.05) urinary excretion of gamma-CEHC, and elevated (P < 0.05) gamma-tocopherol concentrations in tissues and serum of rats fed gamma-tocopherol. These data suggest that sesame seed and its lignans elevate gamma-tocopherol concentration due to the inhibition of CYP3A-dependent metabolism of gamma-tocopherol.